Effects of Sacubitril/Valsartan Across the Spectrum of Renal Impairment in Patients With Heart Failure
- PMID: 38588927
- DOI: 10.1016/j.jacc.2024.03.392
Effects of Sacubitril/Valsartan Across the Spectrum of Renal Impairment in Patients With Heart Failure
Abstract
Background: The Kidney Disease Improving Global Outcomes (KDIGO) classification integrates both estimated glomerular filtration rate and urine-albumin-creatinine ratio to stratify risk more comprehensively in patients with chronic kidney disease. There are limited data assessing whether this classification system is associated with prognosis and treatment response in heart failure populations.
Objectives: The aim of this study was to evaluate the relative treatment effects of sacubitril/valsartan across the KDIGO risk categories in patients with HFrEF.
Methods: PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) was a global randomized controlled trial evaluating sacubitril/valsartan vs enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Patients were classified according to low, moderate, and high/very high KDIGO risk. Treatment responses were assessed according to baseline KDIGO risk. The primary outcome was a composite of cardiovascular (CV) death or heart failure hospitalization. A renal composite outcome was defined as sustained decline in estimated glomerular filtration rate by ≥40% or end-stage kidney disease.
Results: Among 1,910 (23% of total) participants with available data, 42%, 32%, and 26% were classified as low, moderate, and high/very high KDIGO risk, respectively. Patients in the highest KDIGO risk categories experienced the highest rates of the primary composite outcome (7.6 per 100 person-years [95% CI: 6.5-9.0 per 100 person-years], 9.4 per 100 person-years [95% CI: 7.9-11.2 per 100 person-years], and 14.9 per 100 person-years [95% CI: 12.7-17.6 per 100 person-years]; P < 0.001). Sacubitril/valsartan had a similar safety profile and demonstrated consistent effects on the risk of both the primary outcome (PInteraction = 0.31) and the renal composite outcome (PInteraction = 0.50) across the spectrum of KDIGO risk.
Conclusions: One in 4 patients with HFrEF were classified as at least high KDIGO kidney risk; these individuals faced concordantly the highest risks of CV events. Sacubitril/valsartan exhibited consistent CV and kidney protective benefits as well as safety across the spectrum of baseline kidney risk. These data further support initiation of sacubitril/valsartan in HFrEF across a broad range of kidney risk. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255).
Keywords: KDIGO category; heart failure with reduced ejection fraction; kidney function; sacubitril/valsartan.
Copyright © 2024. Published by Elsevier Inc.
Conflict of interest statement
Funding Support and Author Disclosures PARADIGM-HF was funded by Novartis Pharmaceuticals. Dr Chatur is supported by the Canadian Arthur J.E. Child’s Cardiology Fellowship. Dr Neuen has received fees for advisory boards, steering committee roles, scientific presentations, and travel support from AstraZeneca, Bayer, Boehringer Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, the Limbic, Medscape, and Janssen, with all honoraria paid to The George Institute for Global Health. Dr Claggett has been a consultant for Amgen, AO Biome, Biogen, Boehringer Ingelheim, Corvia, Gilead, Myokardia, Cardurion, and Novartis. Dr Beldhuis is supported by the Junior Clinical Scientist Grant from the Dutch Heart Foundation; and her employer is supported by an unrestricted medical grant from Novartis. Dr Mc Causland has received research funding from NIDDK, Satellite Healthcare, Fifth Eye, Novartis, and Lexicon paid directly to his institution; has received consulting fees from GlaxoSmithKline and Zydus Therapeutics; and has received expert witness fees from Rubin-Anders Scientific. Dr Desai has received research grant support from Abbott, AstraZeneca, Alnylam, Bayer, and Novartis; and has received consulting fees and/or honoraria from Abbott, AstraZeneca, Alnylam, Axon Therapeutics, Avidity Biopharma, Bayer, Biofourmis, GlaxoSmithKline, Merck, Novartis, Parexel, Regeneron, River2Renal, Roche, Verily, Veristat, and Zydus. Dr Rouleau has received consulting fees from AstraZeneca. Dr Zile has received fees for serving on a steering committee from Abbott and Ironwood Pharma; has received consulting fees from Boston Scientific and MyoKardia; has received grant support and fees for serving on a steering committee from CVRx and Medtronic; has received fees for serving on an eligibility committee from EBR Systems and V-Wave; has received fees for serving on a clinical events committee from Endotronics; and has received fees for serving on a data and safety monitoring board from Merck. Dr Lefkowitz is an employee of Novartis. Dr Packer has received consulting fees from 89bio, Abbvie, Actavis, Alderlyx, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra. Dr McMurray has received grants and his employer paid by AstraZeneca, Theracos, and GlaxoSmithKline during the conduct of the study; has received grants and his employer being paid by Novartis, Amgen, Bristol Myers Squibb, Bayer, Abb-vie, Dal-Cor, Kidney Research UK, and Cardurion; and has received grants from British Heart Foundation. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. Dr Vaduganathan has received research grant support, has served on advisory boards, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics.
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